5 research outputs found
A new look at the pathogenesis of asthma
No full textAsthma is an inflammatory disorder of the conducting airways that has strong association with allergic sensitization. The disease is characterized by a polarized Th-2 (T-helper-2)-type T-cell response, but in general targeting this component of the disease with selective therapies has been disappointing and most therapy still relies on bronchodilators and corticosteroids rather than treating underlying disease mechanisms. With the disappointing outcomes of targeting individual Th-2 cytokines or manipulating T-cells, the time has come to re-evaluate the direction of research in this disease. A case is made that asthma has its origins in the airways themselves involving defective structural and functional behaviour of the epithelium in relation to environmental insults. Specifically, a defect in barrier function and an impaired innate immune response to viral infection may provide the substrate upon which allergic sensitization takes place. Once sensitized, the repeated allergen exposure will lead to disease persistence. These mechanisms could also be used to explain airway wall remodelling and the susceptibility of the asthmatic lung to exacerbations provoked by respiratory viruses, air pollution episodes and exposure to biologically active allergens. Variable activation of this epithelial-mesenchymal trophic unit could also lead to the emergence of different asthma phenotypes and a more targeted approach to the treatment of these. It also raises the possibility of developing treatments that increase the lung's resistance to the inhaled environment rather than concentrating all efforts on trying to suppress inflammation once it has become established.<br/
Biomarkers in asthmatic inflammation: a study of pharmacological immunomodulation, in vitro and in vivo.
No full textThe effect of macrolides on allergic rhinitis versus chronic rhinosinusitis- an in-vitro study
No full textPhDBackground
The mechanisms of the rhinitic process are complex. Previous studies upon nasal
epithelial cells have begun to investigate rhinitis. HNECs from turbinate explant
tissue were taken from three patient groups (Normals, Chronic Rhinosinusitics and
Rhinitics).
Aims
The study, firstly, aims to establish fundamental differences in cytokine activity
between allergic rhinitis and chronic rhinosinusitis by analysing baseline levels
of cytokines IL-6 and IL-8 and subsequent impact of bacterial endotoxin.
Secondly the study analyses the affect of macrolides on activity in each subgroup.
Methods
HNECs were grown from the biopsy specimens as explant culture. Standardised
exposures to LPS bacterial endotoxin and macrolide were carried out. The
concentration of each mediator present in the medium at the end of incubation
was assessed by ELISA). A final quantity of total cellular protein was obtained.
3
Results
Baseline levels of IL-6 in unstimulated Allergic Rhinitics are
significantly higher than in Normal patients. Baseline levels of IL-8, however, are
lowest in Allergics. LPS significantly stimulates Allergics to increase production
of both IL-6 and IL-8. Macrolides lower IL-6 and IL-8 in both stimulated and
unstimulated AR cells.
Baseline levels of IL-6 and IL-8 are higher in CRS than AR and Normals. LPS
significantly raises IL-6 and IL-8 in CRS. Macrolides increase IL-6 and IL-8 in
stimulated CRS cells however reduce levels of both in un-stimulated cells.
Discussion
Pre-existing neutrophilic and eosinophilic activity in CRS subjects may explain the
increased baseline levels of both cytokines upon macrolide exposure.
Whilst some studies have suggested macrolides act as antimicrobial, others have
suggested that it is their anti-inflammatory effects that are more relevant.
Treatment for Allergic Rhinitis needs to be effective long-term. The results here
are novel and encourage further research to improve understanding of the effects of
macrolides in a potentially pivotal role
Utility of newer technologies for the diagnosis of active and latent tuberculosis
No full textIncludes bibliographical references (leaves 91-109).Since the 1800s the tuberculin skin test (TST) has been the only available test for latent tuberculosis (LTBI). Recently, interferon-gamma release assays (IGRAs) have been developed which are based upon the responses of peripheral blood effector cells to M.tb-specific antigens [early secretory antigenic target -6 (ESAT-6) and culture filtrate protein (CFP10)]. Discordance between the TST and IGRAs has been well documented but remains largely unexplained
